title: Galactomannan-guided preemptive vs. empirical antifungals in the persistently febrile neutropenic patient: a prospective randomized study.
abstract: BACKGROUND
  Patients with neutropenic fever after 4-7 days of broad-spectrum antibiotics are given antifungals empirically. This strategy may lead to over-treatment.
  
  
  METHODS
  Patients with hematological malignancies undergoing intensive chemotherapy or hematopoietic stem cell transplantation were randomized to two arms. Patients in the 'preemptive' arm had regular galactomannan (GM) assays, and received caspofungin, amphotericin or voriconazole (CAV) for persistent febrile neutropenia if they had two positive GM results, or a positive GM result and a computed tomography (CT) of the thorax suggestive of invasive pulmonary aspergillosis (IPA). Patients in the 'empirical' arm received CAV in accordance with established guidelines.
  
  
  RESULTS
  Of 27 episodes in the preemptive arm, two cases of IPA were picked up by monitoring. In six episodes, CAV was started despite persistently negative GM readings. One additional patient received CAV for a false-positive GM. Of 25 episodes in the empirical arm, CAV was started empirically in 10, one of whom had CT features of IPA. By intent-to-treat and evaluable-episode analyses, respectively, the preemptive approach saved 11% and 14% of patients from empirical antifungals. Twelve-week survival was 85.2% in the preemptive arm and 84% in the empirical arm.
  
  
  CONCLUSIONS
  A preemptive approach may reduce empirical antifungal use without compromising survival in persistently febrile neutropenic patients.
authors.affiliation: Department of Infectious Diseases, Singapore General Hospital, Singapore 169608. tan.ban.hock@sgh.com.sg
authors.forename: Ban Hock
authors.initials: BH
authors.lastname: Tan
authors.forename: Jenny Guek Hong
authors.initials: JG
authors.lastname: Low
authors.forename: Nidhi L
authors.initials: NL
authors.lastname: Chlebicka
authors.forename: Asok
authors.initials: A
authors.lastname: Kurup
authors.forename: Foong Koon
authors.initials: FK
authors.lastname: Cheah
authors.forename: Raymond Tzer Pin
authors.initials: RT
authors.lastname: Lin
authors.forename: Yeow Tee
authors.initials: YT
authors.lastname: Goh
authors.forename: Gee Chuan
authors.initials: GC
authors.lastname: Wong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000077336:Caspofungin; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005334:Fever / Q000503:physiopathology; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D016867:Immunocompromised Host; D055744:Invasive Pulmonary Aspergillosis / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D055666:Lipopeptides; D008297:Male; D008351:Mannans / Q000097:blood*; D008875:Middle Aged; D009181:Mycoses / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000517:prevention & control; D009503:Neutropenia / Q000150:complications*; D009894:Opportunistic Infections / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use; D013902:Radiography, Thoracic; D012307:Risk Factors; D012846:Singapore; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008351:Mannans; D011743:Pyrimidines; D014230:Triazoles; C068538:liposomal amphotericin B; C012990:galactomannan; D000666:Amphotericin B; D000077336:Caspofungin; D065819:Voriconazole; D005690:Galactose